Which conditions increase BBB permeability, allowing highly lipophilic drugs to cross?

Which conditions increase BBB permeability, allowing highly lipophilic drugs to cross?

• A. Inflammation only
• B. Underdevelopment only
• C. Both inflammation and developmental immaturity
• D. None of the above

Answer: (C)

The main idea is that the blood-brain barrier becomes more permeable when its protective tight junctions are compromised or not fully developed, allowing lipophilic drugs to slip through more easily. Highly lipophilic drugs cross the BBB mainly by passive diffusion through the endothelial cell membranes, but this diffusion is normally kept in check by tight junctions and by efflux transporters. Inflammation releases cytokines and other mediators that disrupt those tight junctions and can alter transporter activity, increasing paracellular and transcellular passage into the brain. In the developing brain, the barrier is not fully mature; tight junctions are weaker and efflux systems may be underexpressed, leading to higher CNS exposure. So both inflammation and developmental immaturity raise BBB permeability, making the combination the best explanation for greater entry of highly lipophilic drugs. The other options miss either the inflammatory component, the developmental component, or both.

The main idea is that the blood-brain barrier becomes more permeable when its protective tight junctions are compromised or not fully developed, allowing lipophilic drugs to slip through more easily. Highly lipophilic drugs cross the BBB mainly by passive diffusion through the endothelial cell membranes, but this diffusion is normally kept in check by tight junctions and by efflux transporters. Inflammation releases cytokines and other mediators that disrupt those tight junctions and can alter transporter activity, increasing paracellular and transcellular passage into the brain. In the developing brain, the barrier is not fully mature; tight junctions are weaker and efflux systems may be underexpressed, leading to higher CNS exposure. So both inflammation and developmental immaturity raise BBB permeability, making the combination the best explanation for greater entry of highly lipophilic drugs. The other options miss either the inflammatory component, the developmental component, or both.